Recombinant herpes simplex virus type 1 (HSV-1) glycoproteins B (gB) and D (gD) were used as immunotherapeutic agents for the treatment of recurrent genital herpes in guinea pigs. Administration of a gBgD vaccine eight to 21 days after intravaginal HSV-2 inoculation significantly increased the titer of anti-HSV antibodies (P less than 0.005) while significantly reducing the frequency of subsequent herpetic recurrences (P less than 0.05). The effectiveness of gBgD immunotherapy was influenced by both the co-administration of adjuvant, the type of adjuvant, and by the timing and route of administration. These data demonstrate that recurrent HSV disease in animals with established latent infection may be favorably altered by the administration of immunogenic viral proteins.